Right ventricular function declines prior to left ventricular ejection fraction in hypertrophic cardiomyopathy.

BACKGROUND: The right ventricle (RV) in hypertrophic cardiomyopathy (HCM) tends to be neglected, as previous efforts have predominantly focused on examining the prognostic value of left ventricular (LV) abnormalities. The objectives of this study were to assess RV function in HCM, changes over time, and association with clinical outcomes. METHODS: Two hundred and ninety HCM patients with preserved LV ejection fraction (LVEF ≥ 55%) and 30 age- and sex-matched controls underwent cardiovascular magnetic resonance (CMR). All patients were followed up for clinical events for a median duration of 4.4 years. Sixty-three patients had a follow-up CMR undertaken at a median interval of 5.4 years. Main study measures and outcomes were RV function (RV ejection fraction (RVEF) and RV strain) at baseline, temporal changes in RV function over time and prognostic value of RV dysfunction for predicting cardiovascular outcomes in HCM. RESULTS: When compared to controls, HCM patients exhibited lower RV and LV peak global longitudinal systolic strains on feature-tracking analysis of cine images, while RVEF and LVEF were within the normal range. On follow-up CMR, both RV and LV strain parameters decreased over time. RVEF decreased at follow-up (65 ± 7% to 62 ± 7%, P < 0.001) but the change in LVEF was not significant (68 ± 10% to 66 ± 8%, P = 0.30). On clinical follow up, reduced RVEF was an independent predictor of non-sustained ventricular tachycardia (NSVT) [HR 1.10 (95% CI 1.06-1.15), P < 0.001] and composite cardiovascular events (NSVT, stroke, heart failure hospitalisation and cardiovascular death) [HR 1.07 (95% CI 1.03-1.10), P < 0.001]. RV longitudinal strain was an independent predictor of NSVT [HR 1.05 (95% CI 1.01-1.09), P = 0.029]. Patients with RVEF < 55% showed an increased risk of NSVT and composite cardiovascular events. In contrast, LVEF and LV global longitudinal strain were not predictive of such events on multivariable analysis. CONCLUSIONS: In HCM, RV function, including RV strain, and LV strain decrease over time despite preserved LVEF. Reduction in RV but not LV function is associated with adverse cardiovascular outcomes. Assessing RV function in early HCM disease might have a role in risk stratification to prevent future cardiovascular events.

Incremental value of left atrial booster and reservoir strain in predicting atrial fibrillation in patients with hypertrophic cardiomyopathy: a cardiovascular magnetic resonance study.

BACKGROUND: Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. METHODS: We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. RESULTS: Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79-15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81-7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24-5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. CONCLUSIONS: LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.

Producing 3D printed high-fidelity retroperitoneal models from in vivo patient data: The Oxford Method.

Macroscopic anatomy has traditionally been taught using cadaveric material, lectures and a variable amount of additional resources such as online modules. Anatomical models have also been used to assist in teaching. Of these, traditional plastic models have been shown to be effective educational tools, yet have significant drawbacks such as a lack of anatomical detail and texturisation. Three-dimensional (3D) printed models stand to solve these problems and widen access to high-quality anatomical teaching. This paper outlines the use of 3D multi-planar imaging (CT and MRI) as a framework to develop an accurate model of the retroperitoneum. CT and MRI scans were used to construct a virtual 3D model of the retroperitoneum. This was printed locally as a full-size colour model for use in medical education. We give a complete account of the processes and software used. This study is amongst the first of a series in which we will document the newly formed Oxford Library of Anatomy. This series will provide the methodology for the production of models from CT and MRI scans, and the Oxford Library of Anatomy will provide a complete series of some of the most complex anatomical areas and ones which degrade quickly when a real cadaver is being used. In our own internal experience, the models are highly accurate, reproducible and durable, as compared to prosected specimens. We hope they will form an important adjunct in the teaching of the subject.

Differing Impact of Preterm Birth on the Right and Left Atria in Adulthood.

Background Preterm birth affects 10% of live births and is associated with an altered left ventricular and right ventricular phenotype and increased cardiovascular disease risk in young adulthood. Because left atrial (LA) and right atrial (RA) volume and function are known independent predictors of cardiovascular outcomes, we investigated whether these were altered in preterm-born young adults. Methods and Results Preterm-born (n=200) and term-born (n=266) adults aged 18 to 39 years underwent cardiovascular magnetic resonance imaging. LA and RA maximal and minimal volumes (absolute, indexed to body surface area, and as a ratio to ventricular volumes) were obtained to study atrial morphology, while LA and RA stroke volume, strain, and strain rate were used to assess atrial function. Secondary analyses consisted of between-group comparisons based on degree of prematurity. Absolute RA volumes and RA volumes indexed to right ventricular volumes were significantly smaller in preterm-born compared with term-born adults. In addition, RA reservoir and booster strain were higher in preterm-born adults, possibly indicating functional compensation for the smaller RA volumes. LA volumes indexed to left ventricular volumes were significantly greater in preterm-born adults as compared with term-born adults, although absolute LA volumes were similar between groups. LA and RA changes were observed across gestational ages in the preterm group but were greatest in those born very-to-extremely preterm. Conclusions Preterm-born adults show changes in LA and RA structure and function, which may indicate subclinical cardiovascular disease. Further research into underlying mechanisms, opportunities for interventions, and their prognostic value is warranted.

A genome-wide association analysis identifies 16 novel susceptibility loci for carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is a common and disabling condition of the hand caused by entrapment of the median nerve at the level of the wrist. It is the commonest entrapment neuropathy, with estimates of prevalence ranging between 5-10%. Here, we undertake a genome-wide association study (GWAS) of an entrapment neuropathy, using 12,312 CTS cases and 389,344 controls identified in UK Biobank. We discover 16 susceptibility loci for CTS with p < 5 × 10-8. We identify likely causal genes in the pathogenesis of CTS, including ADAMTS17, ADAMTS10 and EFEMP1, and using RNA sequencing demonstrate expression of these genes in surgically resected tenosynovium from CTS patients. We perform Mendelian randomisation and demonstrate a causal relationship between short stature and higher risk of CTS. We suggest that variants within genes implicated in growth and extracellular matrix architecture contribute to the genetic predisposition to CTS by altering the environment through which the median nerve transits.

Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.

Aims: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (

Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults.

BACKGROUND: Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk. OBJECTIVES: The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise. METHODS: We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing. RESULTS: Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m2 vs. 1,669 ± 937 ml/min/m2; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively). CONCLUSIONS: Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231).

Biochar lowers ammonia emission and improves nitrogen retention in poultry litter composting.

The poultry industry produces abundant quantities of nutrient-rich litter, much of which is composted before use as a soil amendment. However, a large proportion of nitrogen (N) in poultry litter is lost via volatilisation during composting, with negative environmental and economic consequences. This study examined the effect of incorporating biochar during composting of poultry litter on ammonia (NH3) volatilisation and N retention. Biochars produced at 550°C from greenwaste (GWB) and poultry litter (PLB) feedstocks were co-composted with a mixture of raw poultry litter and sugarcane straw [carbon (C):N ratio 10:1] in compost bins. Ammonia emissions accounted for 17% of the total N (TN) lost from the control and 12-14% from the biochar-amended compost. The TN emitted as NH3, as a percentage of initial TN, was significantly lower (P<0.05) i.e. by 60% and 55% in the compost amended with GWB and PLB, respectively, relative to the control. The proportion of N retained in the finished compost, as a percentage of initial TN, was 84%, 78% and 67% for the GWB, PLB and nil biochar control, respectively. Lower concentration of dissolved organic C (DOC) together with higher activity of beta-glucosidase and leucine-aminopeptidase were found in the GWB-amended compost (cf. control). It is hypothesized that lower NH3 emission in the GWB-amended compost was caused not just by the higher surface area of this biochar but could also be related to greater incorporation of ammonium (NH4+) in organic compounds during microbial utilisation of DOC. Furthermore, the GWB-amended compost retained more NH4+ at the end of composting than the PLB-amended compost. Results showed that addition of biochar, especially GWB, generated multiple benefits in composting of poultry litter: decrease of NH3 volatilisation, decrease in NH3 toxicity towards microorganisms, and improved N retention, thus enhancing the fertiliser value of the composted litter. It is suggested that the latter benefit is linked to a beneficial modification of the microbial environment.

Biochar increases nitrogen retention and lowers greenhouse gas emissions when added to composting poultry litter.

Biochar has intrinsic and nascent structural and sorption properties that may alter the physical and chemical properties of a composting mixture thus influencing the production of greenhouse gases [GHGs; nitrous oxide (N2O) and methane (CH4)]. In this study, contrasting biochars produced from greenwaste (GWB) or poultry litter (PLB) were incorporated into a composting mixture containing poultry litter and straw, and GHG emissions were measured in situ during composting using Fourier Transform Infrared Spectroscopy (FTIR). Emissions of N2O from the biochar-amended composting mixtures decreased significantly (P<0.05) soon after commencement of the composting process compared with the non-amended control. The cumulative emissions of N2O over 8weeks in the GWB composting mixture (GWBC), PLB composting mixture (PLBC) and control (no biochar) were 4.2, 5.0 and 14.0gN2O-Nkg-1 of total nitrogen (TN) in composting mixture, respectively (P<0.05). The CH4 emissions were significantly (P<0.05) lower in the GWBC and PLBC treatments than the control during the period from day 8 to day 36, when anaerobic conditions likely prevailed. The cumulative CH4 emissions were 12, 18 and 80mg CH4-Ckg-1 of total carbon (TC) for the GWBC, PLBC and control treatments, respectively, though due to wide variation between replicates this difference was not statistically significant. The cumulative N2O and CH4 emissions were similar between the GWBC and PLBC despite differences in properties of the two biochars. X-ray Photoelectron Spectroscopy (XPS) analysis and SEM imaging of the composted biochars indicated the presence of iron oxide compounds and amine-NH3 on the surface and pores of the biochars (PLB>GWB). The change in nitrogen (N) functional groups on the biochar surface after composting is evidence for sorption and/or reaction with N from labile organic N, mineral N, and gaseous N (e.g. N2O). The concentration of NH4+ increased during the thermophilic phase and then decreased during the maturation phase, while NO3- accumulated during the maturation phase. Total N retained was significantly (P<0.05) higher in the PLBC (740g) and the GWBC (660g) relative to the control (530g). The TC retained was significantly higher in the GWBC (10.0kg) and the PLBC (8.5kg) cf. the control (6.0kg). Total GHG emissions across the composting period were 50, 63 and 183kg CO2-eqt-1 of initial mass of GWBC, PLBC and control (dry weight basis) respectively. These results support the co-composting of biochar to lower net emissions of GHGs while increasing N retention (and fertiliser N value) in the mature compost.

Performance, litter quality and gaseous odour emissions of broilers fed phytase supplemented diets.

The effect of graded levels of phytase on performance, bone characteristics, excreta/litter quality and odorant emissions was examined using 720 Ross 308 male d-old broilers. A 2 × 4 factorial arrangement of treatments was employed with 6 replicates of 15 birds per pen. Factors were: diets-positive and negative control (PC, NC); phytase - 0, 500, 1,000, 1,500 FTU/kg. The PC was formulated to meet the 2014 Ross 308 nutrient specifications, whereas the NC was formulated with lower Ca (-1.4 g/kg), available P (-1.5 g/kg), Na (-0.3 g/kg), dLys (-0.2 g/kg) and MEn (-0.28 MJ/kg) equivalent to nutrient matrix values for 500 FTU/kg phytase in the starter, grower and finisher periods (i.e., downspec diet). On d 24, phytase decreased FCR by 1.6, 4.3 and 4.6 points at inclusion levels of 500, 1,000 and 1,500 FTU/kg, respectively (P < 0.01) across all diets. Phytase by diet interactions on BW gain were observed on d 24 and 35 (P < 0.01). The effect of phytase was much more pronounced in the NC diet as compared with the PC diet. On d 24, phytase increased BW gain by 37, 55 and 68 g in the PC and 127, 233 and 173 g in the NC at 500, 1,000 and 1,500 FTU/kg, respectively. Diet by phytase interactions were also observed for tibia ash, litter quality and water to feed intake ratio (P < 0.01) with higher phytase effect in NC as compared with PC. Neither diet nor phytase impacted excreta moisture content on d 18 or 21 (P > 0.05). Solid phase micro-extraction gas chromatography-mass spectrometry (SPME-GC-MS) analysis of gaseous emissions on d 39 indicated no difference in the emission of alcohols, aldehydes, ketones, volatile fatty acids and phenols between treatments (P > 0.05). The results indicate that phytase has greater benefits when formulated using nutrient matrix values as compared with adding it over the top in an already nutrient sufficient diet. The later method would be expected to increase feed costs without concomitant performance benefits.

Dietary composition affects odour emissions from meat chickens.

Abatement of odour emissions has become an important consideration to agricultural industries, including poultry production. The link between diet and odour emissions was studied in two experiments using Ross 308 male meat chickens reared in specially designed chambers in a climate controlled room. In the first experiment, two treatments were compared using three replicates of two birds per chamber. Two wheat-soy based treatment diets were formulated with or without canola seed, an ingredient rich in sulfur amino acids. Treatment 1 (T1) had 13.39 MJ/kg ME (as fed) and used 60 g/kg canola seed without corn while Treatment 2 (T2) contained 12.90 MJ/kg ME (as fed) and used 150 g/kg corn without canola seed. In the second experiment, birds were assigned to three dietary treatments of five replicates with five birds per replicate (chamber). The basal starter, grower and finisher diets in the control group (SBM group) contained soybean meal in the range of 227-291 g/kg (as fed) as the main protein source. The other treatments (CM and MBM groups) contained either high levels of canola meal (174-190 g/kg) or meat meal (74-110 g/kg) at the expense of soybean meal. In both experiments, diets were isocaloric, isonitrogenous and contained similar digestible amino acid contents as per 2007 Aviagen Ross 308 guidelines. Emissions of odour were measured using Fourier transform infrared (FTIR) spectroscopy. In both experiments, major odorous compounds detected included 2,3-butanedione (diacetyl), 2-butanone, dimethyl disulfide, methyl mercaptan, ethyl mercaptan, 2-butanol, 3-methyl-butanal, phenol and m-cresol. In the first experiment, T1 (with canola seed) produced higher concentration of methyl mercaptan (P < 0.05) and lower diacetyl (P < 0.01) than T2. In the second experiment, methyl mercaptan emission was higher in SBM group (P = 0.01) and total elemental sulfur were higher in SBM and CM groups up to day 24 (P < 0.01). Results of these experiments indicated a direct link between diet and odour emissions from meat chickens.